Myelodysplastic Syndromes Clinical Trial
Official title:
A Phase III Randomized, Multicenter Trial Comparing Sirolimus/Tacrolimus With Tacrolimus/Methotrexate as Graft-versus-Host Disease (GVHD) Prophylaxis After HLA-Matched, Related Peripheral Blood Stem Cell Transplantation (BMT CTN #0402)
Verified date | December 2022 |
Source | Medical College of Wisconsin |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The study is designed as a phase III, randomized, open label, multicenter, prospective, comparative trial of sirolimus and tacrolimus versus tacrolimus and methotrexate as graft-versus-host disease (GVHD) prophylaxis after human leukocyte antigen (HLA)-matched, related, peripheral blood stem cell transplantation in individuals with hematologic cancer. Participants will be stratified by transplant center and will be randomly assigned to the sirolimus/tacrolimus or tacrolimus/methotrexate arms at a 1:1 ratio.
Status | Completed |
Enrollment | 304 |
Est. completion date | October 2015 |
Est. primary completion date | October 2012 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 2 Years to 60 Years |
Eligibility | Inclusion Criteria: - 6/6 HLA-matched sibling, defined by Class I (HLA-A and B) serologic typing (or higher resolution) and Class II (HLA-DRBI) molecular typing, who is willing to donate peripheral blood stem cells, and meets institutional criteria for stem cell donation. The donor must be medically eligible to donate stem cells, according to individual transplant center criteria. Pediatric patients for whom a pediatric sibling donor is not anticipated to be a suitable leukapheresis candidate are not eligible. - Karnofsky performance status of at least 70% or Lansky performance status of at least 70% for participants less than 16 years old - For participants less than 18 years old, willing and able to take oral medications, per the treating physician's recommendations Exclusion Criteria: - Prior allogeneic or autologous transplant using any hematopoietic stem cell source - Seropositive for the human immunodeficiency virus (HIV) - Uncontrolled bacterial, viral, or fungal infection (currently taking medication and progression of clinical symptoms) - Pregnant (positive serum human chorionic gonadotropin [ß-HCG] test) or breastfeeding within 4 weeks of study entry - Kidney function: serum creatinine outside the normal range for age, or measured creatinine clearance less than 50 mL/min/1.72m^2 within 4 weeks of study entry - Liver function: most recent direct bilirubin, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) greater than two times the upper limit of normal within 4 weeks of study entry - Lung disease: in adults, forced vital capacity (FVC) or forced expiratory volume in one second (FEV1) less than 60% of predicted value (corrected for hemoglobin); in children, overt hypoxemia, as measured by an oxygen saturation of less than 92% within 4 weeks of study entry - Cardiac ejection fraction of less than 45% in adults and children, or less than 26% shortening fraction in children within 4 weeks of study entry - Cholesterol level greater than 500 mg/dL or triglyceride level greater than 500 mg/dL while being treated, or not on appropriate lipid-lowering therapy within 4 weeks of study entry - Prior history of allergy to sirolimus - Requires voriconazole at time of study entry - Currently receiving another investigational drug unless cleared by the protocol officer or protocol chair - Participants with a history of cancer, other than resected basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent for more than 5 years previously will be allowed. Cancer treated with curative intent for less than 5 years previously will not be allowed unless approved by the protocol officer or protocol chair. |
Country | Name | City | State |
---|---|---|---|
France | Hopital Saint-Louis | Paris | |
United States | University of Michigan Medical Center | Ann Arbor | Michigan |
United States | Emory University | Atlanta | Georgia |
United States | DFCI/Brigham & Women's Hospital | Boston | Massachusetts |
United States | Roswell Park Cancer Institute | Buffalo | New York |
United States | University Hospitals of Cleveland/Case Western | Cleveland | Ohio |
United States | Ohio State, Arthur G. James Cancer Hospital | Columbus | Ohio |
United States | City of Hope National Medical Center | Duarte | California |
United States | Duke University Medical Center | Durham | North Carolina |
United States | University of Florida College of Medicine (Shands) | Gainesville | Florida |
United States | Indiana University Medical Center | Indianapolis | Indiana |
United States | University of Iowa Hospitals and Clinics | Iowa City | Iowa |
United States | UCSD Medical Center | La Jolla | California |
United States | University of Wisconsin Hospital & Clinics | Madison | Wisconsin |
United States | University of Minnesota | Minneapolis | Minnesota |
United States | University of Oklahoma Medical Center | Oklahoma City | Oklahoma |
United States | University of Pennsylvania Cancer Center | Philadelphia | Pennsylvania |
United States | University of Pittsburgh Cancer Institute | Pittsburgh | Pennsylvania |
United States | Oregon Health & Science University | Portland | Oregon |
United States | Virginia Commonwealth University/MCV Hospital | Richmond | Virginia |
United States | Mayo Clinic | Rochester | Minnesota |
United States | Washington University/Barnes Jewish Hospital | Saint Louis | Missouri |
United States | Texas Transplant Institute | San Antonio | Texas |
United States | Stanford Hospital and Clinics | Stanford | California |
Lead Sponsor | Collaborator |
---|---|
Medical College of Wisconsin | Blood and Marrow Transplant Clinical Trials Network, National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI) |
United States, France,
Cutler C, Logan B, Nakamura R, Johnston L, Choi S, Porter D, Hogan WJ, Pasquini M, MacMillan ML, Hsu JW, Waller EK, Grupp S, McCarthy P, Wu J, Hu ZH, Carter SL, Horowitz MM, Antin JH. Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis aft — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Rate of Grades II-IV Acute GVHD-free Survival | The primary objective is to compare rates of 114-day Grades II-IV acute GVHD-free survival post randomization for HLA-matched, related donor allogeneic peripheral blood stem cell transplantation using two different GVHD prophylaxis regimens. Participants are graded on a scale of 1 to 4 according to their symptoms and organs involved, where 4 represents a worse grade. | Day 114 | |
Secondary | Incidence of Acute GVHD | Cumulative incidence of acute GVHD (grade II-IV) occurring 100 days from transplantation. | Measured at Day 100 | |
Secondary | Time to Neutrophil and Platelet Engraftment | Neutrophil engraftment is defined as achieving an Absolute Neutrophil Count (ANC) > 500/mcL for three consecutive measurements on different days. Platelet engraftment is defined as a platelet count > 20,000/mcL for three consecutive measurements over three or more days. | Measured through Day 100 | |
Secondary | Mucositis Severity | Mucositis severity will be scored per the modified Oral Mucositis Assessment Scale (OMAS) scoring system on a scale of 0 - 4, where 0 equals normal mucosa and 4 represents severe mucosa. | Measured at Day 21 | |
Secondary | Rate of Veno-occlusive Disease (VOD) | VOD will be defined as the occurrence of VOD (based on the Baltimore Criteria for the diagnosis of VOD) in conjunction with other end-organ dysfunction. | Measured through Day 100 | |
Secondary | Thrombotic Microangiopathy (TMA) Infection | The occurrence of TMA within the first 100 days after stem cell transplantation will be recorded. The first day of onset will be used for reporting purposes. | Measured through Day 100 | |
Secondary | Reactivation of Cytomegalovirus (CMV) Infection | Measured at Year 2 | ||
Secondary | Treatment-related Mortality | Measured at Day 100 and Year 2 | ||
Secondary | Malignant Disease Relapse | Testing for recurrent malignancy in the blood, marrow or other sites will be used to assess relapse after transplantation. For the purpose of this study, relapse is defined by either morphological or cytogenetic evidence of AML, ALL, CML, MDS or CMML consistent with pre-transplant features. | Measured at Year 2 | |
Secondary | Overall Survival | Measured at Year 2 | ||
Secondary | Infections | Measured at Year 2 | ||
Secondary | Time to Discharge After Transplant | Measured at Year 2 |
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